Bottom Line:
Additionally, despite a global decrease in the B cell population, we observed an increase in both B-1a and marginal zone (MZ)-like B cells.Accumulation of these cells in the liver was associated with an increase in chemokine expression.Further research is required to evaluate the possible cause of their failure to clear the infection within the liver, including the potential role of dysfunctional mitogen-activated protein kinase (MAPK) signaling.

Affiliation: Department of Infectious Diseases and Pathology, College of Veterinary Medicine, University of Florida, Gainesville, FL 32608, USA. collioun@ufl.edu.

ABSTRACTIngestion of Bacillus anthracis results in rapid gastrointestinal (GI) infection, known as GI anthrax. We previously showed that during GI anthrax, there is swift deterioration of intestinal barrier function leading to translocation of gut-associated bacteria into systemic circulation. Additionally, we described dysfunction in colonic B cells. In concordance with our previous studies, here, we report early migration of the Sterne strain of B. anthracis along with other gut-resident bacteria into the infected murine liver. Additionally, despite a global decrease in the B cell population, we observed an increase in both B-1a and marginal zone (MZ)-like B cells. Both of these cell types are capable of producing immunoglobulins against common pathogens and commensals, which act as a general antibody barrier before an antigen-specific antibody response. Accumulation of these cells in the liver was associated with an increase in chemokine expression. These data suggest that the presence of Sterne and other commensals in the liver trigger migration of MZ-like B cells from the spleen to the liver to neutralize systemic spread. Further research is required to evaluate the possible cause of their failure to clear the infection within the liver, including the potential role of dysfunctional mitogen-activated protein kinase (MAPK) signaling.

Mentions:
Due to deficiency of the complement component, C5a, the A/J strain of mice is susceptible to infection with B. anthracis Sterne [11], which lacks the capsule that protects the bacteria against phagocytosis [12]. Mice were gavaged with B. anthracis Sterne spores (109 CFU/mouse) to evaluate the disease process. Two days post-infection, A/J mice began to exhibit lethargy and signs of dyspnea. At day 14, 9/13 (69.2%) of infected mice succumbed to infection (p = 0.008) (Figure S1). We had reported earlier that Sterne infection in mice leads to a decline in intestinal barrier function, resulting in the systemic spread of the Sterne bacterium and gut-associated bacteria [9]; thus, we sought to evaluate bacterial spread within the liver. We quantified the presence of B. anthracis, Enterobacteriaceae, Bifidobacterium, and Bacteroidetes by quantitative real-time PCR (qRT-PCR) using specific primer sets in the livers and the spleens of mice five days post-infection (Figure 1B). In the livers of the orally infected mice, those bacteria were present in significant number at day five post-infection compared to the control mice; however, only the Sterne strain (B. anthracis) and Enterobacteriaceae were increased in number in the spleen at that time point. The increased presence of bacterial species in the liver suggests a route of dissemination via the portal vein. The liver is a unique organ in that it receives blood from two sources, (1) from the general circulation of oxygenated blood via the hepatic artery and (2) from the portal vein that delivers absorbed nutrients for further processing via hepatocellular enzymes [13]. The portal vein not only brings nutrients from the intestines, it also infuses the liver with metabolites generated at intestinal locations, bacterial products like lipopolysaccharide (LPS), and sometimes, intact bacteria [14]. The survival of bacteria in the liver is limited due to the presence of capable immune cells, such as Kupffer cells, hepatocytes, and T and B lymphocytes [13,15]; however, during a breach in the intestinal epithelial barrier, a significant number of gut bacteria has been observed and can contribute to liver pathology, including cirrhosis [16,17]. Similar to previously described intestinal pathology, GI Sterne infection resulted in a compromised intestinal barrier, allowing the bacteria normally contained within the intestinal lumen to enter the systemic circulation via the portal vein.

Mentions:
Due to deficiency of the complement component, C5a, the A/J strain of mice is susceptible to infection with B. anthracis Sterne [11], which lacks the capsule that protects the bacteria against phagocytosis [12]. Mice were gavaged with B. anthracis Sterne spores (109 CFU/mouse) to evaluate the disease process. Two days post-infection, A/J mice began to exhibit lethargy and signs of dyspnea. At day 14, 9/13 (69.2%) of infected mice succumbed to infection (p = 0.008) (Figure S1). We had reported earlier that Sterne infection in mice leads to a decline in intestinal barrier function, resulting in the systemic spread of the Sterne bacterium and gut-associated bacteria [9]; thus, we sought to evaluate bacterial spread within the liver. We quantified the presence of B. anthracis, Enterobacteriaceae, Bifidobacterium, and Bacteroidetes by quantitative real-time PCR (qRT-PCR) using specific primer sets in the livers and the spleens of mice five days post-infection (Figure 1B). In the livers of the orally infected mice, those bacteria were present in significant number at day five post-infection compared to the control mice; however, only the Sterne strain (B. anthracis) and Enterobacteriaceae were increased in number in the spleen at that time point. The increased presence of bacterial species in the liver suggests a route of dissemination via the portal vein. The liver is a unique organ in that it receives blood from two sources, (1) from the general circulation of oxygenated blood via the hepatic artery and (2) from the portal vein that delivers absorbed nutrients for further processing via hepatocellular enzymes [13]. The portal vein not only brings nutrients from the intestines, it also infuses the liver with metabolites generated at intestinal locations, bacterial products like lipopolysaccharide (LPS), and sometimes, intact bacteria [14]. The survival of bacteria in the liver is limited due to the presence of capable immune cells, such as Kupffer cells, hepatocytes, and T and B lymphocytes [13,15]; however, during a breach in the intestinal epithelial barrier, a significant number of gut bacteria has been observed and can contribute to liver pathology, including cirrhosis [16,17]. Similar to previously described intestinal pathology, GI Sterne infection resulted in a compromised intestinal barrier, allowing the bacteria normally contained within the intestinal lumen to enter the systemic circulation via the portal vein.

Bottom Line:
Additionally, despite a global decrease in the B cell population, we observed an increase in both B-1a and marginal zone (MZ)-like B cells.Accumulation of these cells in the liver was associated with an increase in chemokine expression.Further research is required to evaluate the possible cause of their failure to clear the infection within the liver, including the potential role of dysfunctional mitogen-activated protein kinase (MAPK) signaling.

Affiliation:
Department of Infectious Diseases and Pathology, College of Veterinary Medicine, University of Florida, Gainesville, FL 32608, USA. collioun@ufl.edu.

ABSTRACTIngestion of Bacillus anthracis results in rapid gastrointestinal (GI) infection, known as GI anthrax. We previously showed that during GI anthrax, there is swift deterioration of intestinal barrier function leading to translocation of gut-associated bacteria into systemic circulation. Additionally, we described dysfunction in colonic B cells. In concordance with our previous studies, here, we report early migration of the Sterne strain of B. anthracis along with other gut-resident bacteria into the infected murine liver. Additionally, despite a global decrease in the B cell population, we observed an increase in both B-1a and marginal zone (MZ)-like B cells. Both of these cell types are capable of producing immunoglobulins against common pathogens and commensals, which act as a general antibody barrier before an antigen-specific antibody response. Accumulation of these cells in the liver was associated with an increase in chemokine expression. These data suggest that the presence of Sterne and other commensals in the liver trigger migration of MZ-like B cells from the spleen to the liver to neutralize systemic spread. Further research is required to evaluate the possible cause of their failure to clear the infection within the liver, including the potential role of dysfunctional mitogen-activated protein kinase (MAPK) signaling.